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J. Biol. Chem., Vol. 283, Issue 1, 194-201, January 4, 2008
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From the Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030
During infection, damage can occur to the host as an outcome of both pathogen virulence mechanisms and host defense strategies. Using aggregation of a model polyglutamine-containing protein as an indicator in Caenorhabditis elegans, we show that protein damage occurs specifically at the site of the host-pathogen interaction, the intestine, in response to various bacterial pathogens. We demonstrate that the insulin signaling pathway and the heat shock transcription factor (HSF-1) influence the amount of aggregation that occurs, in addition to heat shock proteins and oxidative stress enzymes. We also show that addition of the antioxidants epigallocatechin gallate and
-lipoic acid reduces polyglutamine aggregation. The influence of oxidative stress enzymes and exogenous antioxidants on protein aggregation suggests that reactive oxygen species produced by the host are a source of protein damage during infection. We propose a model in which heat shock proteins and oxidative stress enzymes regulated by insulin signaling and HSF-1 are required for tissue protection during infection, to minimize the effects of protein damage occurring as a result of host-pathogen interactions.
Received for publication, September 24, 2007
* This work was supported by a New Scholar Award in Global Infectious Disease (to D. A. G.) from the Ellison Medical Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: 6431 Fannin St., MSB 1.168, Houston, TX 77030. Tel.: 713-500-5454; Fax: 713-500-5499; E-mail: Danielle.A.Garsin{at}uth.tmc.edu.
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